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SİNERJİSTİK İLAÇ KOMBİNASYONLARININ ANALİZİNDE GÜNCEL MATEMATİKSEL VE İSTATİSTİKSEL YÖNTEMLER

Year 2023, , 687 - 704, 20.05.2023
https://doi.org/10.33483/jfpau.1180259

Abstract

Amaç: İlaç kombinasyon tedavisi, kanser gibi çeşitli ölümcül hastalıkların tedavisinde önemli rol oynamaktadır. İlaçlar kombine edildiğinde sinerjistik, additif veya antagonistik etkileşimler meydana gelir. Bu etkileşimlerin tanımlanması ve ilaç kombinasyonlarının kantitatif analizi basit değildir. Terminoloji, deneysel protokoller ve modellerin yanı sıra veri analizinde standardizasyon eksikliği başlıca sorunlardır. Bu çalışmada, sinerjistik ilaç kombinasyonlarının incelenmesi ve analizi ile ilgili mevcut matematiksel ve istatistiksel yöntemler derlenmiştir. Takibinde, yaygın kullanılan yöntemleri anlamak için gerekli olan farmakolojik ve matematiksel kavramlar da derlenmiş, avantaj ve dezavantajları tartışılmıştır. Son olarak ilaç kombinasyonlarının analizinde dikkat edilmesi gereken temel konular açıklanmıştır.
Sonuç ve Tartışma: Muhtemel tüm deneysel koşullar için uygun optimum bir model olmadığı için, ilaç kombinasyonlarının kantitatif analizinin, burada tartışılan farklı yaklaşımların kollektif kullanımı ile kolaylaşacağını umuyoruz. Bu çalışmanın ilaç kombinasyonlarının analizi için bir referans teşkil edeceğine inanıyoruz.

Supporting Institution

Çalışma herhangi bir kurum tarafından desteklenmemiştir.

References

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CURRENT MATHEMATICAL AND STATISTICAL METHODS IN THE ANALYSIS OF SYNERGISTIC DRUG COMBINATIONS

Year 2023, , 687 - 704, 20.05.2023
https://doi.org/10.33483/jfpau.1180259

Abstract

Objective: Combination drug therapy plays an important role in treating various deadly diseases such as cancer. When drugs are combined, synergistic, additive or antagonistic interactions occur. The determination of these interactions and the quantitative analysis of drug combinations are not simple. The lack of standardization in terminology, experimental protocols, and models as well as data analysis are major challenges. In this study, the current mathematical and statistical methods concerning the study and analysis of synergistic drug combinations are reviewed. Following, the pharmacological and mathematical concepts necessary to understand the widely used methods are also reviewed, and their advantages and disadvantages are discussed. Finally, the main issues to be considered in the analysis of drug combinations are explained.
Result and Discussion: Because there is no optimal suitable model for all possible experimental conditions, we hope that the quantitative analysis of drug combinations will be facilitated by the collective use of the different approaches discussed here. We believe that this study will serve as a reference for the analysis of drug combinations.

References

  • 1. Mokhtari, R.B., Homayouni, T.S., Baluch, N., Morgatskaya, E., Kumar, S., Das, B., Yeger, H. (2017). Combination therapy in combating cancer. Oncotarget, 8(23), 38022-38043. [CrossRef]
  • 2. Frei, E., Holland, J.F., Schneiderman, M.A., Pinkel, D., Selkirk, G., Freireich, E.J., Silver, R.T., Gold, G.L., Regelson, W. (1958). A comparative study of two regimens of combination chemotherapy in acute leukemia. Blood, 13(12), 1126-1148. [CrossRef]
  • 3. Xie, Y.H., Chen, Y.X., Fang, J.Y. (2020). Comprehensive review of targeted therapy for colorectal cancer. Signal Transduction and Targeted Therapy, 5(1), 1-30. [CrossRef]
  • 4. Lawrence, M.S., Stojanov, P., Mermel, C.H., Robinson, J.T., Garraway, L.A., Golub, T.R., Meyerson, M., Gabriel, S.B., Lander, E.S., Getz, G. (2014). Discovery and saturation analysis of cancer genes across 21 tumour types. Nature, 505(7484), 495-501. [CrossRef]
  • 5. Lazikani, B.A., Banerji, U., Workman, P. (2012). Combinatorial drug therapy for cancer in the post-genomic era. Nature Biotechnology, 30(7), 679-692. [CrossRef]
  • 6. Sun, X., Vilar, S., Tatonetti, N.P. (2013). High-throughput methods for combinatorial drug discovery. Science Translational Medicine, 5(205), 205rv1-205rv1. [CrossRef]
  • 7. Gibbs, B.K., Sourbier, C. (2018) Detecting the potential pharmacological synergy of drug combination by viability assays in vitro, Chaperones. 129-137. [CrossRef]
  • 8. Niu, J., Straubinger, R.M., Mager, D.E. (2019). Pharmacodynamic drug–drug Interactions. Clinical Pharmacology &Therapeutics, 105(6), 1395-1406. [CrossRef]
  • 9. Pinto, A.C., Moreira, J.N., Simões, S. (2011) Combination chemotherapy in cancer: Principles, evaluation and drug delivery strategies, in Current Cancer Treatment-Novel Beyond Conventional Approaches, IntechOpen, 693-714. [CrossRef]
  • 10. Foucquier, J., Guedj, M. (2015). Analysis of drug combinations: current methodological landscape. Pharmacology Research & Perspectives, 3(3), e00149. [CrossRef]
  • 11. Chou, T.C. (2006). Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacological Reviews, 58(3), 621-681. [CrossRef]
  • 12. Pemovska, T., Bigenzahn, J.W., Furga, G.S. (2018). Recent advances in combinatorial drug screening and synergy scoring. Current Opinion in Pharmacology, 42, 102-110. [CrossRef]
  • 13. Roell, K.R., Reif, D.M., Reif, A.A.M. (2017). An introduction to terminology and methodology of chemical synergy-perspectives from across disciplines. Frontiers in Pharmacology, 8, 158. [CrossRef]
  • 14. Duarte, D., Vale, N. (2022). Evaluation of synergism in drug combinations and reference models for future orientations in oncology. Current Research in Pharmacology and Drug Discovery, 100110. [CrossRef]
  • 15. Nieuwenhuis, S., Forstmann, B.U., Wagenmakers, E.J. (2011). Erroneous analyses of interactions in neuroscience: a problem of significance. Nature Neuroscience, 14(9), 1105-1107. [CrossRef]
  • 16. Lehár, J., Zimmermann, G.R., Krueger, A.S., Molnar, R.A., Ledell, J.T., Heilbut, A.M., Short, G.F., Giusti, L.C., Nolan, G.P., Magid, O.A. (2007). Chemical combination effects predict connectivity in biological systems. Molecular Systems Biology, 3(1), 80. [CrossRef]
  • 17. Vlot, A.H., Aniceto, N., Menden, M.P., Merzenich, G.U., Bender, A. (2019). Applying synergy metrics to combination screening data: agreements, disagreements and pitfalls. Drug Discovery Today, 24(12), 2286-2298. [CrossRef]
  • 18. Slinker, B.K. (1998). The statistics of synergism. Journal of Molecular and Cellular Cardiology, 30(4), 723-731. [CrossRef]
  • 19. Caudle, R.M., Williams, G.M. (1993). The misuse of analysis of variance to detect synergy in combination drug studies. Pain, 55(3), 313-317. [CrossRef]
  • 20. Goldoni, M., Johansson, C. (2007). A mathematical approach to study combined effects of toxicants in vitro: evaluation of the Bliss independence criterion and the Loewe additivity model. Toxicology in Vitro, 21(5), 759-769. [CrossRef]
  • 21. Özer, B.O. (2021). Ph.D. Thesis. Development of new nanotherapeutic modalities for the treatment of colon cancer. Department of Biotechnology and Genetics, Institute of Natural Sciences, Trakya University, Edirne, Turkey.
  • 22. Zhao, W., Sachsenmeier, K., Zhang, L., Sult, E., Hollingsworth, R.E., Yang, H. (2014). A new bliss independence model to analyze drug combination data. Journal of Biomolecular Screening, 19(5), 817-821. [CrossRef]
  • 23. Gessner, P.K. (1974). The isobolographic method applied to drug interactions. Drug interactions, (pp.349-362). New York, NY: Raven Press.
  • 24. Gessner, P.K. (1988). A straightforward method for the study of drug interactions: an isobolographic analysis primer. Journal of the American College of Toxicology, 7(7), 987-1012. [CrossRef]
  • 25. Frei, W. (1913). Versuche über kombination von desinfektionsmitteln. Medical Microbiology and Immunology, 75(1), 433-496. [CrossRef]
  • 26. Tallarida, R.J. (2012). Revisiting the isobole and related quantitative methods for assessing drug synergism. Journal of Pharmacology and Experimental Therapeutics, 342(1), 2-8. [CrossRef]
  • 27. Berenbaum, M.C. (1977). Synergy, additivism and antagonism in immunosuppression-critical review. Clinical & Experimental Immunology, 28(1), 1-18.
  • 28. Chou, T.-C., Talalay, P. (1984). Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Advances in Enzyme Regulation, 22, 27-55. [CrossRef]
  • 29. Greco, W.R., Bravo, G., Parsons, J.C. (1995). The search for synergy: a critical review from a response surface perspective. Pharmacological Reviews, 47(2), 331-385.
  • 30. Grabovsky, Y., Tallarida, R.J. (2004). Isobolographic analysis for combinations of a full and partial agonist: curved isoboles. Journal of Pharmacology and Experimental Therapeutics, 310(3), 981-986. [CrossRef]
  • 31. Chou, T.-C. (2008). Preclinical versus clinical drug combination studies. Leukemia & Lymphoma, 49(11), 2059-2080. [CrossRef]
  • 32. Chou, T.-C. (2011). The mass-action law based algorithms for quantitative econo-green bio-research. Integrative Biology, 3(5), 548-559. [CrossRef]
  • 33. Bijnsdorp, I.V., Giovannetti, E., Peters, G.J. (2011) Analysis of drug interactions, in Cancer Cell Culture, Springer: Humana Press. 421-434. [CrossRef]
  • 34. Chou, T.-C., Shapiro, T.A., Fu, J., Chou, J.H., Merzenich, G.S.U. (2019). Computerized quantification of drugs synergism in animal studies or in clinical trials using only ten data points. Synergy, 9, 100049. [CrossRef]
  • 35. Ashton, J.C. (2015). Drug combination studies and their synergy quantification using the Chou-Talalay method-Letter. Cancer Research, 75(11), 2400-2400. [CrossRef]
  • 36. Xu, S.P., Sun, G.P., Shen, Y.X., Peng, W.R., Wang, H., Wei, W. (2007). Synergistic effect of combining paeonol and cisplatin on apoptotic induction of human hepatoma cell lines 1. Acta Pharmacologica Sinica, 28(6), 869-878. [CrossRef]
  • 37. Yadav, B., Wennerberg, K., Aittokallio, T., Tang, J. (2015). Searching for drug synergy in complex dose-response landscapes using an interaction potency model. Computational and Structural Biotechnology Journal, 13, 504-513. [CrossRef]
  • 38. Twarog, N.R., Martinez, N.E., Gartrell, J., Xie, J., Tinkle, C.L., Shelat, A.A. (2021). Using response surface models to analyze drug combinations. Drug Discovery Today, 26(8), 2014-2024. [CrossRef]
  • 39. Twarog, N.R., Stewart, E., Hammill, C.V., Shelat, A.A. (2016). BRAID: a unifying paradigm for the analysis of combined drug action. Scientific Reports, 6(1), 1-15. [CrossRef]
  • 40. Spinozzi, G., Tini, V., Ferrari, A., Gionfriddo, I., Ranieri, R., Milano, F., Pierangeli, S., Donnini, S., Mezzasoma, F., Silvestri, S. (2022). SiCoDEA: a simple, fast and complete app for analyzing the effect of individual drugs and their combinations. Biomolecules, 12(7), 904. [CrossRef]
  • 41. Du, D., Chang, C.H., Wang, Y., Tong, P., Chan, W.K., Chiu, Y., Peng, B., Tan, L., Weinstein, J.N., Lorenzi, P.L. (2019). Response envelope analysis for quantitative evaluation of drug combinations. Bioinformatics, 35(19), 3761-3770. [CrossRef]
  • 42. Doern, C.D. (2014). When does 2 plus 2 equal 5? A review of antimicrobial synergy testing. Journal of Clinical Microbiology, 52(12), 4124-4128. [CrossRef]
  • 43. Berthoud, H.R. (2013). Synergy: a concept in search of a definition. Endocrinology, 154(11), 3974-3977. [CrossRef]
  • 44. Ocana, A., Amir, E., Yeung, C., Seruga, B., Tannock, I. (2012). How valid are claims for synergy in published clinical studies? Annals of Oncology, 23(8), 2161-2166. [CrossRef]
  • 45. Steel, G.G., Peckham, M.J. (1979). Exploitable mechanisms in combined radiotherapy-chemotherapy: The concept of additivity. International Journal of Radiation Oncology Biology Physics, 5(1), 85-91. [CrossRef]
  • 46. Jia, J., Zhu, F., Ma, X., Cao, Z.W., Li, Y.X., Chen, Y.Z. (2009). Mechanisms of drug combinations: interaction and network perspectives. Nature Reviews Drug Discovery, 8(2), 111-128. [CrossRef]
  • 47. Box, G.E., Draper, N.R. (1987). Empirical model-building and response surfaces. Wiley Series in Probability & Statistics, John Wiley & Sons, New York, p.424.
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There are 65 citations in total.

Details

Primary Language Turkish
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Collection
Authors

Bayram Oğuz Özer 0000-0003-2833-3133

Early Pub Date May 17, 2023
Publication Date May 20, 2023
Submission Date September 26, 2022
Acceptance Date February 2, 2023
Published in Issue Year 2023

Cite

APA Özer, B. O. (2023). SİNERJİSTİK İLAÇ KOMBİNASYONLARININ ANALİZİNDE GÜNCEL MATEMATİKSEL VE İSTATİSTİKSEL YÖNTEMLER. Journal of Faculty of Pharmacy of Ankara University, 47(2), 687-704. https://doi.org/10.33483/jfpau.1180259
AMA Özer BO. SİNERJİSTİK İLAÇ KOMBİNASYONLARININ ANALİZİNDE GÜNCEL MATEMATİKSEL VE İSTATİSTİKSEL YÖNTEMLER. Ankara Ecz. Fak. Derg. May 2023;47(2):687-704. doi:10.33483/jfpau.1180259
Chicago Özer, Bayram Oğuz. “SİNERJİSTİK İLAÇ KOMBİNASYONLARININ ANALİZİNDE GÜNCEL MATEMATİKSEL VE İSTATİSTİKSEL YÖNTEMLER”. Journal of Faculty of Pharmacy of Ankara University 47, no. 2 (May 2023): 687-704. https://doi.org/10.33483/jfpau.1180259.
EndNote Özer BO (May 1, 2023) SİNERJİSTİK İLAÇ KOMBİNASYONLARININ ANALİZİNDE GÜNCEL MATEMATİKSEL VE İSTATİSTİKSEL YÖNTEMLER. Journal of Faculty of Pharmacy of Ankara University 47 2 687–704.
IEEE B. O. Özer, “SİNERJİSTİK İLAÇ KOMBİNASYONLARININ ANALİZİNDE GÜNCEL MATEMATİKSEL VE İSTATİSTİKSEL YÖNTEMLER”, Ankara Ecz. Fak. Derg., vol. 47, no. 2, pp. 687–704, 2023, doi: 10.33483/jfpau.1180259.
ISNAD Özer, Bayram Oğuz. “SİNERJİSTİK İLAÇ KOMBİNASYONLARININ ANALİZİNDE GÜNCEL MATEMATİKSEL VE İSTATİSTİKSEL YÖNTEMLER”. Journal of Faculty of Pharmacy of Ankara University 47/2 (May 2023), 687-704. https://doi.org/10.33483/jfpau.1180259.
JAMA Özer BO. SİNERJİSTİK İLAÇ KOMBİNASYONLARININ ANALİZİNDE GÜNCEL MATEMATİKSEL VE İSTATİSTİKSEL YÖNTEMLER. Ankara Ecz. Fak. Derg. 2023;47:687–704.
MLA Özer, Bayram Oğuz. “SİNERJİSTİK İLAÇ KOMBİNASYONLARININ ANALİZİNDE GÜNCEL MATEMATİKSEL VE İSTATİSTİKSEL YÖNTEMLER”. Journal of Faculty of Pharmacy of Ankara University, vol. 47, no. 2, 2023, pp. 687-04, doi:10.33483/jfpau.1180259.
Vancouver Özer BO. SİNERJİSTİK İLAÇ KOMBİNASYONLARININ ANALİZİNDE GÜNCEL MATEMATİKSEL VE İSTATİSTİKSEL YÖNTEMLER. Ankara Ecz. Fak. Derg. 2023;47(2):687-704.

Kapsam ve Amaç

Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.